Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE247019 | GEO | 2024/08/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cancer-associated DNA hypermethylation of Polycomb targets requires DNMT3A dual recognition of histone H2AK119 ubiquitination and the nucleosome acidic patch.

Project description:During tumor development, promoter CpG islands that are normally silenced by Polycomb repressive complexes (PRCs) become DNA-hypermethylated. The molecular mechanism by which de novo DNA methyltransferase(s) [DNMT(s)] catalyze CpG methylation at PRC-regulated regions remains unclear. Here, we report a cryo-electron microscopy structure of the DNMT3A long isoform (DNMT3A1) amino-terminal region in complex with a nucleosome carrying PRC1-mediated histone H2A lysine-119 monoubiquitination (H2AK119Ub). We identify regions within the DNMT3A1 amino terminus that bind H2AK119Ub and the nucleosome acidic patch. This bidentate interaction is required for effective DNMT3A1 engagement with H2AK119Ub-modified chromatin in cells. Further, aberrant redistribution of DNMT3A1 to Polycomb target genes recapitulates the cancer-associated DNA hypermethylation signature and inhibits their transcriptional activation during cell differentiation. This effect is rescued by disruption of the DNMT3A1-acidic patch interaction. Together, our analyses reveal a binding interface critical for mediating promoter CpG island DNA hypermethylation, a major molecular hallmark of cancer.

| S-EPMC11352909 | biostudies-literature

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [CUT7Run]

Project description:During tumor development, promoter CpG islands (CGIs) that are normally silenced by Polycomb repressive complexes (PRCs) become DNA hypermethylated. The molecular mechanism by which de novo DNA methyltransferase(s) catalyze CpG methylation at PRC-regulated regions remains unclear. Here we report a cryo-EM structure of DNMT3A long isoform (DNMT3A1) N-terminal region in complex with nucleosome carrying PRC1-mediated histone H2A lysine 119 mono-ubiquitination (H2AK119Ub). We identify regions within the DNMT3A1 N-terminus that bind H2AK119Ub and the nucleosome acidic patch. This bidentate interaction is specifically required for effective DNMT3A1 engagement with H2AK119Ub-modified chromatin in cells. Furthermore, aberrant redistribution of DNMT3A1 to Polycomb target genes inhibits their transcriptional derepression during cell differentiation and recapitulates the cancer-associated DNA hypermethylation signature, an effect rescued by disruption of DNMT3A1-acidic patch interaction. Together, our analyses reveal a binding interface critical for countering promoter CGI DNA hypermethylation, a major molecular hallmark of cancer.

2024-08-31 | GSE247016 | GEO

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [RRBS]

2024-08-31 | GSE247013 | GEO

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [ChIP-seq]

2024-08-31 | GSE247015 | GEO

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [RNA-Seq]

2024-08-31 | GSE247014 | GEO

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [EM-Seq]

2024-08-31 | GSE247018 | GEO

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [Cut&Tag]

2024-08-31 | GSE247017 | GEO

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch

Project description:Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch

| PRJNA1035552 | ENA

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [CUT7Run]

Project description:Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [CUT7Run]

| PRJNA1035556 | ENA

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [RRBS]

Project description:Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch [RRBS]

| PRJNA1035554 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data